PXD055410

PXD055410 is an original dataset announced via ProteomeXchange.

Title	AMPK activation promotes transcriptional activation of TFEB through its dephosphorylation
Description	Transcription Factor EB (TFEB) is a critical regulator of lysosomal biogenesis, autophagy and energy homeostasis through regulating expression of genes belonging to the Coordinated Lysosomal Expression and Regulation network. Recently, AMP-activated protein kinase (AMPK) was reported to phosphorylate TFEB at three conserved C-terminal Ser residues (S466, S467, S469) and these phosphorylation events were essential for transcriptional activation of TFEB. In sharp contrast to this proposition, here we demonstrate that AMPK activation leads to dephosphorylation of the C-terminal sites, and that AMPK is dispensable for mTORC1-mediated/torin1-sensitive TFEB activation. We show that a synthetic peptide encompassing C-terminal Ser residues is a poor substrate of AMPK in cell-free assay. Treatment with of cells with AMPK activator (MK-8722) or mTOR inhibitor (torin1) robustly dephosphorylated TFEB not only at mTORC1-targeted N-terminal Ser sites, but also the C-terminal sites. Loss of function of AMPK abrogated MK-8722- but not torin1-induced dephosphorylation and induction of vast majority of TFEB target genes.
HostingRepository	PRIDE
AnnounceDate	2026-02-11
AnnouncementXML	Submission_2026-02-11_03:12:52.016.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Gajanan Sathe
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	phosphorylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-09-01 07:41:47	ID requested
⏵ 1	2026-02-11 03:12:52	announced

10.1080/15548627.2026.2629720;

Negoita F, Fraguas Bringas C, Hellberg K, Luda KM, Liu H, Li Z, Cuenco J, Zhao JF, Sathe G, Ganley IG, Sapkota GP, Sakamoto K, AMPK promotes TFEB transcriptional activity through dephosphorylation at both MTORC1-dependent and -independent sites. Autophagy, ():1-15(2026) [pubmed]

submitter keyword: BAY-3827

coordinated lysosomal expression and regulation

MK-8722

reversible phosphorylation

mTOR

TFE3

Professor Gopal Sapkota
contact affiliation	MRC Investigator MRC Protein Phosphorylation & Ubiquitylation Unit Sir James Black Centre, School of Life Sciences University of Dundee, Dundee DD1 5EH, UK. Phone: ++44 1382 386330
contact email	g.sapkota@dundee.ac.uk
lab head
Gajanan Sathe
contact affiliation	Centre for Targeted Protein Degradation (CeTPD) University of Dundee
contact email	gsathe001@dundee.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD055410
     1. Label: PRIDE project
     2. Name: AMPK activation promotes transcriptional activation of TFEB through its dephosphorylation